Friedreich's Ataxia
Conditions
Brief summary
The objectives of the study are: * To evaluate the safety and tolerability of single and multiple oral doses of VP 20629 in subjects with Friedreich's ataxia (FA). \[Primary\] * To characterize the pharmacokinetics of VP 20629 by investigation of the plasma concentration-time profile following single and multiple oral doses in subjects with FA. \[Secondary\] * To investigate the pharmacodynamic effects of VP 20629 on plasma 8-isoprostane and malondialdehyde and urinary 8-hydroxydeoxyguanosine concentrations following multiple oral doses in subjects with FA. \[Exploratory\]
Interventions
DRUGVP 20629
DRUGPlacebo
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Be 18 to 45 years of age (inclusive). 2. Have a body mass index between 18 and 27 kg/m\^2 (inclusive). 3. Have a clinical presentation consistent with FA. 4. Have a confirmed diagnosis of FA with a defined expanded guanosine, adenine, adenine (GAA) triplet repeat number. 5. Have an International Cooperative Ataxia Rating Scale (ICARS) mean total score of ≤75. 6. If female, be postmenopausal (cessation of menses ≥1 year), surgically sterile, or have a negative serum human chorionic gonadotropin pregnancy test within 5 days prior to the first dose of study drug. Women of child bearing potential must also be on an acceptable method of birth control, as determined by the Investigator, for 3 months prior to the first dose and must agree to continue use through 2 months after the last dose of study drug. If male, be surgically sterile or agree to follow an acceptable method of birth control as determined by the Investigator, from the screening visit through 2 months after the last dose of study drug. 7. Be able to swallow capsules whole. 8. Agree to adhere to the protocol-defined schedule of assessments and procedures. 9. Be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.
Exclusion criteria
1. Have taken coenzyme Q10, idebenone, other dietary or herbal supplements (with an anti-oxidative effect), or over-the-counter medications (including homeopathic medicines and vitamins) within 1 week prior to the first dose of study drug on Day 1. 2. If female, be pregnant or breastfeeding. 3. Have a positive test result for human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C antibody. 4. Have ingested any alcohol within 48 hours before admission to the clinical study unit on Day -1. NOTE: Caffeine intake should be limited to 2 caffeine-containing beverages per day during this same time period. 5. Have participated in an investigational drug trial within 30 days prior to the first dose of study drug on Day 1. NOTE: Subjects who received study drug (VP 20629 or placebo) in a single-dose group in this study and completed the Post-treatment Safety Assessment are allowed to enroll in a multiple-dose group following a 21 day washout period, provided they continue to meet protocol eligibility criteria. Subjects cannot enroll in a multiple-dose group if they have an ongoing adverse event following participation in a single-dose group or had a serious adverse event during a single-dose group (regardless of causality). 6. Have a known hypersensitivity to any ingredient in the study formulation. 7. Have, as determined by the Investigator and/or medical monitor, any clinically relevant medical or surgical condition that could interfere with the administration of study drug, interpretation of study results, or compromise the safety or well-being of the subject. 8. Have a Columbia-Suicide Severity Rating Scale (C-SSRS) score of 4 or 5.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | From Start of Study Treatment up to Day 19 | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs (TEAEs), defined as all AEs that start during study drug treatment (and up to 7 days after the last dose of the study drug) and were not seen at baseline, or were seen at baseline but increased in frequency and/or severity during study drug treatment (and up to 7 days after the last dose of study drug). |
| Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | From Start of Study Treatment up to Day 19 | An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Treatment-emergent were events between first dose of study drug and 7 days after the last dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with Grade 3 or higher treatment-emergent adverse events for laboratory abnormalities were reported as clinically relevant laboratory changes. |
| Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | From Start of Study Treatment up to Day 19 | Vital sign assessments included systolic blood pressure, diastolic blood pressure, heart rate, and temperature. Vital signs abnormalities reported as TEAEs were reported. |
| Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | From Start of Study Treatment up to Day 19 | ECG included PR interval, QRS interval, QTcB interval, QTcF interval were considered as clinically significant ECG abnormalities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, and 8 hours Postdose on Day 1 | The AUC(0-8) is the area under the plasma concentration-time curve from time zero to 8 hours postdose. |
| Area Under the Plasma Concentration Versus Time Curve to the Last Measurable Plasma Concentration (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1 | The AUCt is the measure of the plasma drug concentration from time zero to time t. |
| Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1 | The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z). |
| Total Body Drug Clearance (CL/F) of VP 20629 for Single Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1 | Lambda(z) is first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve. |
| Cumulative Amount Excreted Into the Urine (Ae) for Unchanged VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | 0-4, 4-8, 8-16, 16-24, 24-36 and 36-48 hours postdose on Day 1 | The Ae is the amount of drug excreted in urine. It is calculated by multiplying the urinary volume with the urinary drug concentration. |
| Percentage of Drug Excreted in Urine (Ae%) of VP 20629 for Single Dose Groups | -4, 4-8, 8-16, 16-24, 24-36 and 36-48 hours postdose on Day 1 | The Ae% is the percentage of drug dose excreted into the urine calculated as (Ae divided by dose)∗100. |
| Renal Clearance (CLR) of VP 20629 for Single Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1 | The CLR is the renal clearance of the drug, calculated as Ae/AUC(0-infinity) on Day 1 or Ae(0-24)/AUC(0-24) on Day 1. |
| Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 24 and 72 hours Postdose on Day 1 | The Cmax is the maximum observed plasma concentration of Multiple Dose of VP 20629 and VP 20631. |
| Maximum Observed Serum Concentration at Steady State (Cmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8 | The Cmax,ss is the maximum observed plasma concentration at steady state. |
| Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 24 and 72 hours Postdose on Day 1 | The Tmax is the time to reach maximum observed plasma concentration of multiple dose of VP 20629 and VP 20631. |
| Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1 | The Cmax is the maximum observed plasma concentration of single dose of VP 20629 and VP 20631. |
| Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8 | The AUC is the area under the plasma concentration-time curve observed. |
| Area Under the Plasma Concentration Versus Time Curve at Steady State (AUCss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, and 8 hours Postdose on Day 8 | The AUCss is the area under the plasma concentration time curve observed during a dosing at steady state. |
| Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6 and 8 hours Postdose on Day 1 | The AUC(0-8) is the area under the plasma concentration-time curve from time zero to 8 hours postdose. |
| Area Under the Plasma Concentration Versus Time Curve (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8 | The AUCtau is the measure of the plasma drug concentration from time zero to time t. |
| Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8 | The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z). |
| Volume of Distribution (Vz/F) of VP 20629 for Multiple Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8 | The Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. |
| Total Body Drug Clearance at Steady State (CLss/F) of VP 20629 for Multiple Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8 | Lambda(z) is first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve. |
| Cumulative Amount Excreted Into the Urine at Steady State (Ae,ss) of Unchanged VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | 0-4, 4-8, 8-16, 16-24, 24-36, and 36-48 hours postdose on Day 8 | The Ae,ss is the amount of drug excreted in urine. It is calculated by multiplying the urinary volume with the urinary drug concentration. |
| Percentage of Drug Excreted in Urine at Steady-State (Ae%,ss) of VP 20629 for Multiple Dose Groups | 0-4, 4-8, 8-16, 16-24, 24-36, and 36-48 hours postdose on Day 8 | The Ae%,ss is the percentage of drug dose excreted into the urine calculated as (Ae divided by dose)∗100. |
| Renal Clearance at Steady State (CLR,ss) of VP 20629 for Multiple Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8 | The CLR,ss is the renal clearance of the drug, calculated as Ae/AUC(0-infinity) on Day 8. |
| Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8 | The Tmax,ss is the time to reach maximum observed plasma concentration at steady state of multiple dose of VP 20629 and VP 20631. |
| Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1 | The Tmax is the time to reach maximum observed plasma concentration of single dose of VP 20629 and VP 20631. |
| Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1 | The AUC is the area under the plasma concentration-time curve observed. |
| Volume of Distribution (Vz/F) of VP 20629 for Single Dose Groups | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1 | The Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. |
Countries
United States
Participant flow
Recruitment details
This is a multicenter study conducted between 13 August 2013 and 18 June 2015.
Pre-assignment details
A total of 46 participants were enrolled to the study, of which 32 were randomly assigned to single-dose group and 24 were randomly assigned to multiple-dose group. Participants who received investigational product in a single-dose group and completed the post-treatment safety assessment were allowed to enrol in a multiple-dose group.
Participants by arm
| Arm | Count |
|---|---|
| Single Dose Placebo Participants received placebo matching to single dose of VP 20629 capsules orally under fasting condition on Day 1. | 8 |
| Single Dose VP 20629 150 mg Participants received single dose of VP 20629 capsules of 150 milligram (mg) orally under fasting condition on Day 1. | 6 |
| Single Dose VP 20629 450 mg Participants received single dose of VP 20629 capsules of 450 mg orally under fasting condition on Day 1. | 6 |
| Single Dose VP 20629 900 mg Participants received single dose of VP 20629 capsules of 900 mg orally under fasting condition on Day 1. | 6 |
| Single Dose VP 20629 1200 mg Participants received single dose of VP 20629 capsules of 1200 mg orally under fasting condition on Day 1. | 6 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Multiple Dose Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Multiple Dose Period | Randomized Not Treated | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Single Dose Placebo | Single Dose VP 20629 150 mg | Single Dose VP 20629 450 mg | Single Dose VP 20629 900 mg | Single Dose VP 20629 1200 mg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 25.1 years STANDARD_DEVIATION 7.04 | 22.7 years STANDARD_DEVIATION 1.97 | 27.8 years STANDARD_DEVIATION 4.45 | 28.0 years STANDARD_DEVIATION 6.9 | 26.8 years STANDARD_DEVIATION 8.86 | 26.0 years STANDARD_DEVIATION 6.27 |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 2 Participants | 3 Participants | 4 Participants | 17 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 15 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 |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 8 | 0 / 6 | 4 / 6 | 5 / 6 | 6 / 6 | 4 / 6 | 3 / 6 | 6 / 6 | 3 / 5 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 5 |
Outcome results
Primary
Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs)
ECG included PR interval, QRS interval, QTcB interval, QTcF interval were considered as clinically significant ECG abnormalities.
Time frame: From Start of Study Treatment up to Day 19
Population: The ITT-S set consisted of all participants who were randomly assigned to an investigational product treatment group and who received at least 1 partial or complete dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Dose Placebo | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | 0 participants |
| Single Dose VP 20629 150 mg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | 1 participants |
| Single Dose VP 20629 450 mg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | 0 participants |
| Single Dose VP 20629 900 mg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | 0 participants |
| Single Dose VP 20629 1200 mg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | 0 participants |
| Multiple Dose Placebo | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | 0 participants |
| Multiple Dose VP 20629 300 mg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | 1 participants |
| Multiple Dose VP 20629 600 mg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | 0 participants |
| Multiple Dose VP 20629 900 mg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | 0 participants |
Primary
Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Treatment-emergent were events between first dose of study drug and 7 days after the last dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with Grade 3 or higher treatment-emergent adverse events for laboratory abnormalities were reported as clinically relevant laboratory changes.
Time frame: From Start of Study Treatment up to Day 19
Population: The ITT-S set consisted of all participants who were randomly assigned to an investigational product treatment group and who received at least 1 partial or complete dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single Dose Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood Glucose Increased | 0 participants |
| Single Dose Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil Count Decreased | 0 participants |
| Single Dose VP 20629 150 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil Count Decreased | 0 participants |
| Single Dose VP 20629 150 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood Glucose Increased | 0 participants |
| Single Dose VP 20629 450 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil Count Decreased | 0 participants |
| Single Dose VP 20629 450 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood Glucose Increased | 0 participants |
| Single Dose VP 20629 900 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood Glucose Increased | 0 participants |
| Single Dose VP 20629 900 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil Count Decreased | 0 participants |
| Single Dose VP 20629 1200 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil Count Decreased | 0 participants |
| Single Dose VP 20629 1200 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood Glucose Increased | 1 participants |
| Multiple Dose Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood Glucose Increased | 0 participants |
| Multiple Dose Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil Count Decreased | 0 participants |
| Multiple Dose VP 20629 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood Glucose Increased | 0 participants |
| Multiple Dose VP 20629 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil Count Decreased | 0 participants |
| Multiple Dose VP 20629 600 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil Count Decreased | 1 participants |
| Multiple Dose VP 20629 600 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood Glucose Increased | 0 participants |
| Multiple Dose VP 20629 900 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood Glucose Increased | 0 participants |
| Multiple Dose VP 20629 900 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil Count Decreased | 0 participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs (TEAEs), defined as all AEs that start during study drug treatment (and up to 7 days after the last dose of the study drug) and were not seen at baseline, or were seen at baseline but increased in frequency and/or severity during study drug treatment (and up to 7 days after the last dose of study drug).
Time frame: From Start of Study Treatment up to Day 19
Population: The ITT-safety (ITT-S) set consisted of all participants who were randomly assigned to an investigational product treatment group and who received at least 1 partial or complete dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single Dose Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 3 participants |
| Single Dose Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 0 participants |
| Single Dose VP 20629 150 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 0 participants |
| Single Dose VP 20629 150 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 0 participants |
| Single Dose VP 20629 450 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 0 participants |
| Single Dose VP 20629 450 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 4 participants |
| Single Dose VP 20629 900 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 0 participants |
| Single Dose VP 20629 900 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 5 participants |
| Single Dose VP 20629 1200 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 0 participants |
| Single Dose VP 20629 1200 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 6 participants |
| Multiple Dose Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 4 participants |
| Multiple Dose Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 0 participants |
| Multiple Dose VP 20629 300 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 3 participants |
| Multiple Dose VP 20629 300 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 1 participants |
| Multiple Dose VP 20629 600 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 6 participants |
| Multiple Dose VP 20629 600 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 0 participants |
| Multiple Dose VP 20629 900 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAE | 3 participants |
| Multiple Dose VP 20629 900 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAE | 0 participants |
Primary
Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Vital sign assessments included systolic blood pressure, diastolic blood pressure, heart rate, and temperature. Vital signs abnormalities reported as TEAEs were reported.
Time frame: From Start of Study Treatment up to Day 19
Population: The ITT-S set consisted of all participants who were randomly assigned to an investigational product treatment group and who received at least 1 partial or complete dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Dose Placebo | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | 0 participants |
| Single Dose VP 20629 150 mg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | 0 participants |
| Single Dose VP 20629 450 mg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | 0 participants |
| Single Dose VP 20629 900 mg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | 0 participants |
| Single Dose VP 20629 1200 mg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | 0 participants |
| Multiple Dose Placebo | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | 0 participants |
| Multiple Dose VP 20629 300 mg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | 0 participants |
| Multiple Dose VP 20629 600 mg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | 0 participants |
| Multiple Dose VP 20629 900 mg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | 0 participants |
Secondary
Area Under the Plasma Concentration Versus Time Curve at Steady State (AUCss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
The AUCss is the area under the plasma concentration time curve observed during a dosing at steady state.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, and 8 hours Postdose on Day 8
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Area Under the Plasma Concentration Versus Time Curve at Steady State (AUCss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 | 99794 h*ng/ml | Standard Deviation 44105 |
| Single Dose Placebo | Area Under the Plasma Concentration Versus Time Curve at Steady State (AUCss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 | 2848 h*ng/ml | Standard Deviation 677 |
| Single Dose VP 20629 150 mg | Area Under the Plasma Concentration Versus Time Curve at Steady State (AUCss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 | 138567 h*ng/ml | Standard Deviation 37102 |
| Single Dose VP 20629 150 mg | Area Under the Plasma Concentration Versus Time Curve at Steady State (AUCss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 | 6006 h*ng/ml | Standard Deviation 1215 |
| Single Dose VP 20629 450 mg | Area Under the Plasma Concentration Versus Time Curve at Steady State (AUCss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 | 196587 h*ng/ml | Standard Deviation 18647 |
| Single Dose VP 20629 450 mg | Area Under the Plasma Concentration Versus Time Curve at Steady State (AUCss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 | 9732 h*ng/ml | Standard Deviation 1932 |
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
The AUC(0-8) is the area under the plasma concentration-time curve from time zero to 8 hours postdose.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6 and 8 hours Postdose on Day 1
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, n is number of participants analyzed for this outcome measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=1,6,6,5) | 20 h*ng/mL | — |
| Single Dose Placebo | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,6,6,5) | 1080 h*ng/mL | Standard Deviation 451 |
| Single Dose VP 20629 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=1,6,6,5) | 1926 h*ng/mL | Standard Deviation 315 |
| Single Dose VP 20629 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,6,6,5) | 72054 h*ng/mL | Standard Deviation 21395 |
| Single Dose VP 20629 450 mg | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=1,6,6,5) | 4130 h*ng/mL | Standard Deviation 1137 |
| Single Dose VP 20629 450 mg | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,6,6,5) | 113510 h*ng/mL | Standard Deviation 26091 |
| Single Dose VP 20629 900 mg | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,6,6,5) | 144059 h*ng/mL | Standard Deviation 10302 |
| Single Dose VP 20629 900 mg | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=1,6,6,5) | 5740 h*ng/mL | Standard Deviation 1076 |
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups
The AUC(0-8) is the area under the plasma concentration-time curve from time zero to 8 hours postdose.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, and 8 hours Postdose on Day 1
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N (Number of participants analyzed) and n are number of participants analyzed for this outcome measure and for the specified compound, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 1708 h*ng/mL | Standard Deviation 693 |
| Single Dose Placebo | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 (n=5,6,6,6,6) | 21 h*ng/mL | Standard Deviation 27 |
| Single Dose VP 20629 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 95673 h*ng/mL | Standard Deviation 10720 |
| Single Dose VP 20629 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 (n=5,6,6,6,6) | 3201 h*ng/mL | Standard Deviation 802 |
| Single Dose VP 20629 450 mg | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 183398 h*ng/mL | Standard Deviation 10155 |
| Single Dose VP 20629 450 mg | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 (n=5,6,6,6,6) | 9934 h*ng/mL | Standard Deviation 4155 |
| Single Dose VP 20629 900 mg | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 (n=5,6,6,6,6) | 27426 h*ng/mL | Standard Deviation 8969 |
| Single Dose VP 20629 900 mg | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 302823 h*ng/mL | Standard Deviation 31529 |
| Single Dose VP 20629 1200 mg | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 325019 h*ng/mL | Standard Deviation 45937 |
| Single Dose VP 20629 1200 mg | Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 (n=5,6,6,6,6) | 37258 h*ng/mL | Standard Deviation 19280 |
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
The AUC is the area under the plasma concentration-time curve observed.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 | 184407 h*ng/ml | Standard Deviation 108180 |
| Single Dose Placebo | Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 | 5156 h*ng/ml | Standard Deviation 1869 |
| Single Dose VP 20629 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 | 217115 h*ng/ml | Standard Deviation 58417 |
| Single Dose VP 20629 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 | 9299 h*ng/ml | Standard Deviation 2402 |
| Single Dose VP 20629 450 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 | 332140 h*ng/ml | Standard Deviation 73876 |
| Single Dose VP 20629 450 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 | 14807 h*ng/ml | Standard Deviation 2206 |
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups
The AUC is the area under the plasma concentration-time curve observed.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 | 152277 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 27113 |
| Single Dose Placebo | Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 | 5118 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 1155 |
| Single Dose VP 20629 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 | 14208 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 4117 |
| Single Dose VP 20629 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 | 298443 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 42925 |
| Single Dose VP 20629 450 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 | 463893 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 44896 |
| Single Dose VP 20629 450 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 | 33366 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 9374 |
| Single Dose VP 20629 900 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 | 525976 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 107856 |
| Single Dose VP 20629 900 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 | 48322 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 17989 |
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
The AUCtau is the measure of the plasma drug concentration from time zero to time t.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N (Number of participants analyzed) and n are number of participants analyzed for this outcome measure and for the specified compound, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Area Under the Plasma Concentration Versus Time Curve (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,5,6,5) | 6769 h*ng/mL | Standard Deviation 1480 |
| Single Dose Placebo | Area Under the Plasma Concentration Versus Time Curve (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=4,5,6,5) | 81 h*ng/mL | Standard Deviation 124 |
| Single Dose VP 20629 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=4,5,6,5) | 4992 h*ng/mL | Standard Deviation 1790 |
| Single Dose VP 20629 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,5,6,5) | 177487 h*ng/mL | Standard Deviation 102429 |
| Single Dose VP 20629 450 mg | Area Under the Plasma Concentration Versus Time Curve (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,5,6,5) | 212568 h*ng/mL | Standard Deviation 57087 |
| Single Dose VP 20629 450 mg | Area Under the Plasma Concentration Versus Time Curve (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=4,5,6,5) | 9103 h*ng/mL | Standard Deviation 2358 |
| Single Dose VP 20629 900 mg | Area Under the Plasma Concentration Versus Time Curve (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,5,6,5) | 325464 h*ng/mL | Standard Deviation 72038 |
| Single Dose VP 20629 900 mg | Area Under the Plasma Concentration Versus Time Curve (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=4,5,6,5) | 14570 h*ng/mL | Standard Deviation 2177 |
Secondary
Area Under the Plasma Concentration Versus Time Curve to the Last Measurable Plasma Concentration (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups
The AUCt is the measure of the plasma drug concentration from time zero to time t.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N (Number of participants analyzed) and n are number of participants analyzed for this outcome measure and for the specified compound, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Area Under the Plasma Concentration Versus Time Curve to the Last Measurable Plasma Concentration (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 (n=6,6,6,6,6) | 164 h*ng/mL | Standard Deviation 149 |
| Single Dose Placebo | Area Under the Plasma Concentration Versus Time Curve to the Last Measurable Plasma Concentration (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 9903 h*ng/mL | Standard Deviation 4192 |
| Single Dose VP 20629 150 mg | Area Under the Plasma Concentration Versus Time Curve to the Last Measurable Plasma Concentration (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 (n=6,6,6,6,6) | 4876 h*ng/mL | Standard Deviation 1201 |
| Single Dose VP 20629 150 mg | Area Under the Plasma Concentration Versus Time Curve to the Last Measurable Plasma Concentration (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 147287 h*ng/mL | Standard Deviation 25078 |
| Single Dose VP 20629 450 mg | Area Under the Plasma Concentration Versus Time Curve to the Last Measurable Plasma Concentration (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 294510 h*ng/mL | Standard Deviation 41445 |
| Single Dose VP 20629 450 mg | Area Under the Plasma Concentration Versus Time Curve to the Last Measurable Plasma Concentration (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 (n=6,6,6,6,6) | 14070 h*ng/mL | Standard Deviation 4110 |
| Single Dose VP 20629 900 mg | Area Under the Plasma Concentration Versus Time Curve to the Last Measurable Plasma Concentration (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 457563 h*ng/mL | Standard Deviation 46848 |
| Single Dose VP 20629 900 mg | Area Under the Plasma Concentration Versus Time Curve to the Last Measurable Plasma Concentration (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 (n=6,6,6,6,6) | 33121 h*ng/mL | Standard Deviation 9322 |
| Single Dose VP 20629 1200 mg | Area Under the Plasma Concentration Versus Time Curve to the Last Measurable Plasma Concentration (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 519996 h*ng/mL | Standard Deviation 106355 |
| Single Dose VP 20629 1200 mg | Area Under the Plasma Concentration Versus Time Curve to the Last Measurable Plasma Concentration (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 (n=6,6,6,6,6) | 48114 h*ng/mL | Standard Deviation 17934 |
Secondary
Cumulative Amount Excreted Into the Urine (Ae) for Unchanged VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups
The Ae is the amount of drug excreted in urine. It is calculated by multiplying the urinary volume with the urinary drug concentration.
Time frame: 0-4, 4-8, 8-16, 16-24, 24-36 and 36-48 hours postdose on Day 1
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Cumulative Amount Excreted Into the Urine (Ae) for Unchanged VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 | 55.0 microgram (mcg) | Standard Deviation 17.2 |
| Single Dose Placebo | Cumulative Amount Excreted Into the Urine (Ae) for Unchanged VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 | 131644.9 microgram (mcg) | Standard Deviation 19834.5 |
| Single Dose VP 20629 150 mg | Cumulative Amount Excreted Into the Urine (Ae) for Unchanged VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 | 529022.1 microgram (mcg) | Standard Deviation 92223.8 |
| Single Dose VP 20629 150 mg | Cumulative Amount Excreted Into the Urine (Ae) for Unchanged VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 | 79.4 microgram (mcg) | Standard Deviation 13.3 |
| Single Dose VP 20629 450 mg | Cumulative Amount Excreted Into the Urine (Ae) for Unchanged VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 | 368.6 microgram (mcg) | Standard Deviation 196.3 |
| Single Dose VP 20629 450 mg | Cumulative Amount Excreted Into the Urine (Ae) for Unchanged VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 | 953370.1 microgram (mcg) | Standard Deviation 116994.6 |
| Single Dose VP 20629 900 mg | Cumulative Amount Excreted Into the Urine (Ae) for Unchanged VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 | 518.1 microgram (mcg) | Standard Deviation 105.6 |
| Single Dose VP 20629 900 mg | Cumulative Amount Excreted Into the Urine (Ae) for Unchanged VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 | 1263419.7 microgram (mcg) | Standard Deviation 190242.9 |
Secondary
Cumulative Amount Excreted Into the Urine at Steady State (Ae,ss) of Unchanged VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
The Ae,ss is the amount of drug excreted in urine. It is calculated by multiplying the urinary volume with the urinary drug concentration.
Time frame: 0-4, 4-8, 8-16, 16-24, 24-36, and 36-48 hours postdose on Day 8
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Cumulative Amount Excreted Into the Urine at Steady State (Ae,ss) of Unchanged VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 | 56.8 microgram | Standard Deviation 48.1 |
| Single Dose Placebo | Cumulative Amount Excreted Into the Urine at Steady State (Ae,ss) of Unchanged VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 | 110042 microgram | Standard Deviation 10852 |
| Single Dose VP 20629 150 mg | Cumulative Amount Excreted Into the Urine at Steady State (Ae,ss) of Unchanged VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 | 111.4 microgram | Standard Deviation 27.5 |
| Single Dose VP 20629 150 mg | Cumulative Amount Excreted Into the Urine at Steady State (Ae,ss) of Unchanged VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 | 254540 microgram | Standard Deviation 52440 |
| Single Dose VP 20629 450 mg | Cumulative Amount Excreted Into the Urine at Steady State (Ae,ss) of Unchanged VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 | 283873 microgram | Standard Deviation 78764 |
| Single Dose VP 20629 450 mg | Cumulative Amount Excreted Into the Urine at Steady State (Ae,ss) of Unchanged VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 | 244.3 microgram | Standard Deviation 226.6 |
Secondary
Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
Lambda(z) is first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 | 0.0703 per hour | Standard Deviation 0.0076 |
| Single Dose Placebo | Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 | 0.0693 per hour | Standard Deviation 0.0031 |
| Single Dose VP 20629 150 mg | Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 | 0.0775 per hour | Standard Deviation 0.0094 |
| Single Dose VP 20629 150 mg | Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 | 0.0729 per hour | Standard Deviation 0.0107 |
| Single Dose VP 20629 450 mg | Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 | 0.0777 per hour | Standard Deviation 0.0111 |
| Single Dose VP 20629 450 mg | Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 | 0.0768 per hour | Standard Deviation 0.0085 |
Secondary
Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups
Lambda(z) is first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 | 0.0688 per hour | Standard Deviation 0.0111 |
| Single Dose Placebo | Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 | 0.0615 per hour | Standard Deviation 0.0114 |
| Single Dose VP 20629 150 mg | Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 | 0.0889 per hour | Standard Deviation 0.0046 |
| Single Dose VP 20629 150 mg | Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 | 0.0874 per hour | Standard Deviation 0.0033 |
| Single Dose VP 20629 450 mg | Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 | 0.1007 per hour | Standard Deviation 0.0312 |
| Single Dose VP 20629 450 mg | Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 | 0.0958 per hour | Standard Deviation 0.0295 |
| Single Dose VP 20629 900 mg | Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 | 0.0892 per hour | Standard Deviation 0.0105 |
| Single Dose VP 20629 900 mg | Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 | 0.0972 per hour | Standard Deviation 0.0124 |
Secondary
Maximum Observed Serum Concentration at Steady State (Cmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
The Cmax,ss is the maximum observed plasma concentration at steady state.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N (Number of participants analyzed) and n are number of participants analyzed for this outcome measure and for the specified compound, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Maximum Observed Serum Concentration at Steady State (Cmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,5,6,5) | 212 ng/mL | Standard Deviation 54 |
| Single Dose Placebo | Maximum Observed Serum Concentration at Steady State (Cmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=4,5,6,5) | 5 ng/mL | Standard Deviation 3 |
| Single Dose VP 20629 150 mg | Maximum Observed Serum Concentration at Steady State (Cmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,5,6,5) | 25060 ng/mL | Standard Deviation 10656 |
| Single Dose VP 20629 150 mg | Maximum Observed Serum Concentration at Steady State (Cmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=4,5,6,5) | 754 ng/mL | Standard Deviation 194 |
| Single Dose VP 20629 450 mg | Maximum Observed Serum Concentration at Steady State (Cmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=4,5,6,5) | 1638 ng/mL | Standard Deviation 252 |
| Single Dose VP 20629 450 mg | Maximum Observed Serum Concentration at Steady State (Cmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,5,6,5) | 32583 ng/mL | Standard Deviation 6941 |
| Single Dose VP 20629 900 mg | Maximum Observed Serum Concentration at Steady State (Cmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,5,6,5) | 45000 ng/mL | Standard Deviation 3431 |
| Single Dose VP 20629 900 mg | Maximum Observed Serum Concentration at Steady State (Cmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=4,5,6,5) | 3156 ng/mL | Standard Deviation 1305 |
Secondary
Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
The Cmax is the maximum observed plasma concentration of Multiple Dose of VP 20629 and VP 20631.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 24 and 72 hours Postdose on Day 1
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N (Number of participants analyzed) and n are number of participants analyzed for this outcome measure and for the specified compound, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,6,6,5) | 172 nanogram per milliliter (ng/mL) | Standard Deviation 82 |
| Single Dose Placebo | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=1,6,6,5) | 6 nanogram per milliliter (ng/mL) | — |
| Single Dose VP 20629 150 mg | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=1,6,6,5) | 556 nanogram per milliliter (ng/mL) | Standard Deviation 88 |
| Single Dose VP 20629 150 mg | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,6,6,5) | 21667 nanogram per milliliter (ng/mL) | Standard Deviation 2890 |
| Single Dose VP 20629 450 mg | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,6,6,5) | 30000 nanogram per milliliter (ng/mL) | Standard Deviation 5592 |
| Single Dose VP 20629 450 mg | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=1,6,6,5) | 1270 nanogram per milliliter (ng/mL) | Standard Deviation 446 |
| Single Dose VP 20629 900 mg | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,6,6,5) | 40440 nanogram per milliliter (ng/mL) | Standard Deviation 8878 |
| Single Dose VP 20629 900 mg | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=1,6,6,5) | 2094 nanogram per milliliter (ng/mL) | Standard Deviation 480 |
Secondary
Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups
The Cmax is the maximum observed plasma concentration of single dose of VP 20629 and VP 20631.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N (Number of participants analyzed) and n are number of participants analyzed for this outcome measure and for the specified compound, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 269 nanogram per milliliter (ng/mL) | Standard Deviation 92 |
| Single Dose Placebo | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 (n=6,6,6,6,6) | 7 nanogram per milliliter (ng/mL) | Standard Deviation 2 |
| Single Dose VP 20629 150 mg | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 29350 nanogram per milliliter (ng/mL) | Standard Deviation 6344 |
| Single Dose VP 20629 150 mg | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 (n=6,6,6,6,6) | 1068 nanogram per milliliter (ng/mL) | Standard Deviation 353 |
| Single Dose VP 20629 450 mg | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 47350 nanogram per milliliter (ng/mL) | Standard Deviation 12742 |
| Single Dose VP 20629 450 mg | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 (n=6,6,6,6,6) | 3556 nanogram per milliliter (ng/mL) | Standard Deviation 2347 |
| Single Dose VP 20629 900 mg | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 (n=6,6,6,6,6) | 12515 nanogram per milliliter (ng/mL) | Standard Deviation 6056 |
| Single Dose VP 20629 900 mg | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 76983 nanogram per milliliter (ng/mL) | Standard Deviation 7293 |
| Single Dose VP 20629 1200 mg | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 73717 nanogram per milliliter (ng/mL) | Standard Deviation 14848 |
| Single Dose VP 20629 1200 mg | Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 (n=6,6,6,6,6) | 15842 nanogram per milliliter (ng/mL) | Standard Deviation 12438 |
Secondary
Percentage of Drug Excreted in Urine (Ae%) of VP 20629 for Single Dose Groups
The Ae% is the percentage of drug dose excreted into the urine calculated as (Ae divided by dose)∗100.
Time frame: -4, 4-8, 8-16, 16-24, 24-36 and 36-48 hours postdose on Day 1
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Dose Placebo | Percentage of Drug Excreted in Urine (Ae%) of VP 20629 for Single Dose Groups | 0.0367 percentage of dose | Standard Deviation 0.0115 |
| Single Dose VP 20629 150 mg | Percentage of Drug Excreted in Urine (Ae%) of VP 20629 for Single Dose Groups | 0.0176 percentage of dose | Standard Deviation 0.003 |
| Single Dose VP 20629 450 mg | Percentage of Drug Excreted in Urine (Ae%) of VP 20629 for Single Dose Groups | 0.0410 percentage of dose | Standard Deviation 0.0218 |
| Single Dose VP 20629 900 mg | Percentage of Drug Excreted in Urine (Ae%) of VP 20629 for Single Dose Groups | 0.0432 percentage of dose | Standard Deviation 0.0088 |
Secondary
Percentage of Drug Excreted in Urine at Steady-State (Ae%,ss) of VP 20629 for Multiple Dose Groups
The Ae%,ss is the percentage of drug dose excreted into the urine calculated as (Ae divided by dose)∗100.
Time frame: 0-4, 4-8, 8-16, 16-24, 24-36, and 36-48 hours postdose on Day 8
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Dose Placebo | Percentage of Drug Excreted in Urine at Steady-State (Ae%,ss) of VP 20629 for Multiple Dose Groups | 0.0568 percentage of dose | Standard Deviation 0.0481 |
| Single Dose VP 20629 150 mg | Percentage of Drug Excreted in Urine at Steady-State (Ae%,ss) of VP 20629 for Multiple Dose Groups | 0.0557 percentage of dose | Standard Deviation 0.0138 |
| Single Dose VP 20629 450 mg | Percentage of Drug Excreted in Urine at Steady-State (Ae%,ss) of VP 20629 for Multiple Dose Groups | 0.0814 percentage of dose | Standard Deviation 0.0755 |
Secondary
Renal Clearance at Steady State (CLR,ss) of VP 20629 for Multiple Dose Groups
The CLR,ss is the renal clearance of the drug, calculated as Ae/AUC(0-infinity) on Day 8.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Dose Placebo | Renal Clearance at Steady State (CLR,ss) of VP 20629 for Multiple Dose Groups | 0.0005 liter per hour | Standard Deviation 0.0002 |
| Single Dose VP 20629 150 mg | Renal Clearance at Steady State (CLR,ss) of VP 20629 for Multiple Dose Groups | 0.0009 liter per hour | Standard Deviation 0.0004 |
| Single Dose VP 20629 450 mg | Renal Clearance at Steady State (CLR,ss) of VP 20629 for Multiple Dose Groups | 0.0013 liter per hour | Standard Deviation 0.0013 |
Secondary
Renal Clearance (CLR) of VP 20629 for Single Dose Groups
The CLR is the renal clearance of the drug, calculated as Ae/AUC(0-infinity) on Day 1 or Ae(0-24)/AUC(0-24) on Day 1.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Dose Placebo | Renal Clearance (CLR) of VP 20629 for Single Dose Groups | 0.0003 liter per hour | Standard Deviation 0.0001 |
| Single Dose VP 20629 150 mg | Renal Clearance (CLR) of VP 20629 for Single Dose Groups | 0.0003 liter per hour | Standard Deviation 0.0001 |
| Single Dose VP 20629 450 mg | Renal Clearance (CLR) of VP 20629 for Single Dose Groups | 0.0008 liter per hour | Standard Deviation 0.0005 |
| Single Dose VP 20629 900 mg | Renal Clearance (CLR) of VP 20629 for Single Dose Groups | 0.0010 liter per hour | Standard Deviation 0.0002 |
Secondary
Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 | 9.95 hour | Standard Deviation 1.09 |
| Single Dose Placebo | Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 | 10.01 hour | Standard Deviation 0.44 |
| Single Dose VP 20629 150 mg | Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 | 9.07 hour | Standard Deviation 1.21 |
| Single Dose VP 20629 150 mg | Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 | 9.68 hour | Standard Deviation 1.45 |
| Single Dose VP 20629 450 mg | Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 | 9.11 hour | Standard Deviation 0.96 |
| Single Dose VP 20629 450 mg | Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 | 9.05 hour | Standard Deviation 1.18 |
Secondary
Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups
The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Single Dose Placebo | Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 | 9.98 hour |
| Single Dose Placebo | Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 | 11.19 hour |
| Single Dose VP 20629 150 mg | Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 | 7.85 hour |
| Single Dose VP 20629 150 mg | Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 | 7.87 hour |
| Single Dose VP 20629 450 mg | Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 | 7.43 hour |
| Single Dose VP 20629 450 mg | Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 | 7.72 hour |
| Single Dose VP 20629 900 mg | Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 | 7.85 hour |
| Single Dose VP 20629 900 mg | Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631 | 6.95 hour |
Secondary
Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
The Tmax,ss is the time to reach maximum observed plasma concentration at steady state of multiple dose of VP 20629 and VP 20631.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N (Number of participants analyzed) and n are number of participants analyzed for this outcome measure and for the specified compound, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=4,5,6,5) | 0.50 hour | Standard Deviation 0.71 |
| Single Dose Placebo | Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,5,6,5) | 6.65 hour | Standard Deviation 3.96 |
| Single Dose VP 20629 150 mg | Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=4,5,6,5) | 1.67 hour | Standard Deviation 0.42 |
| Single Dose VP 20629 150 mg | Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,5,6,5) | 0.97 hour | Standard Deviation 0.04 |
| Single Dose VP 20629 450 mg | Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,5,6,5) | 2.00 hour | Standard Deviation 0.32 |
| Single Dose VP 20629 450 mg | Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=4,5,6,5) | 2.26 hour | Standard Deviation 0.53 |
| Single Dose VP 20629 900 mg | Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=4,5,6,5) | 1.90 hour | Standard Deviation 0.89 |
| Single Dose VP 20629 900 mg | Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,5,6,5) | 1.80 hour | Standard Deviation 0.91 |
Secondary
Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
The Tmax is the time to reach maximum observed plasma concentration of multiple dose of VP 20629 and VP 20631.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 24 and 72 hours Postdose on Day 1
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N (Number of participants analyzed) and n are number of participants analyzed for this outcome measure and for the specified compound, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,6,6,5) | 3.24 hour | Standard Deviation 1.72 |
| Single Dose Placebo | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=1,6,6,5) | 0.58 hour | — |
| Single Dose VP 20629 150 mg | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=1,6,6,5) | 1.42 hour | Standard Deviation 0.49 |
| Single Dose VP 20629 150 mg | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,6,6,5) | 1.09 hour | Standard Deviation 0.38 |
| Single Dose VP 20629 450 mg | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,6,6,5) | 1.42 hour | Standard Deviation 0.38 |
| Single Dose VP 20629 450 mg | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=1,6,6,5) | 1.59 hour | Standard Deviation 0.38 |
| Single Dose VP 20629 900 mg | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20629 (n=6,6,6,5) | 1.63 hour | Standard Deviation 0.71 |
| Single Dose VP 20629 900 mg | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups | VP 20631 (n=1,6,6,5) | 2.02 hour | Standard Deviation 0.82 |
Secondary
Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups
The Tmax is the time to reach maximum observed plasma concentration of single dose of VP 20629 and VP 20631.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N (Number of participants analyzed) and n are number of participants analyzed for this outcome measure and for the specified compound, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Dose Placebo | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 9.94 hour | Standard Deviation 7.58 |
| Single Dose Placebo | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631(n=6,6,6,6,6) | 23.71 hour | Standard Deviation 20.17 |
| Single Dose VP 20629 150 mg | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 1.50 hour | Standard Deviation 0.45 |
| Single Dose VP 20629 150 mg | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631(n=6,6,6,6,6) | 2.17 hour | Standard Deviation 0.41 |
| Single Dose VP 20629 450 mg | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 1.92 hour | Standard Deviation 0.95 |
| Single Dose VP 20629 450 mg | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631(n=6,6,6,6,6) | 2.83 hour | Standard Deviation 2.5 |
| Single Dose VP 20629 900 mg | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631(n=6,6,6,6,6) | 2.16 hour | Standard Deviation 0.6 |
| Single Dose VP 20629 900 mg | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 1.83 hour | Standard Deviation 0.61 |
| Single Dose VP 20629 1200 mg | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20629 (n=7,6,6,6,6) | 3.01 hour | Standard Deviation 1.77 |
| Single Dose VP 20629 1200 mg | Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups | VP 20631(n=6,6,6,6,6) | 3.35 hour | Standard Deviation 2.33 |
Secondary
Total Body Drug Clearance at Steady State (CLss/F) of VP 20629 for Multiple Dose Groups
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Dose Placebo | Total Body Drug Clearance at Steady State (CLss/F) of VP 20629 for Multiple Dose Groups | 1.133 liter per hour | Standard Deviation 0.388 |
| Single Dose VP 20629 150 mg | Total Body Drug Clearance at Steady State (CLss/F) of VP 20629 for Multiple Dose Groups | 1.524 liter per hour | Standard Deviation 0.364 |
| Single Dose VP 20629 450 mg | Total Body Drug Clearance at Steady State (CLss/F) of VP 20629 for Multiple Dose Groups | 1.537 liter per hour | Standard Deviation 0.14 |
Secondary
Total Body Drug Clearance (CL/F) of VP 20629 for Single Dose Groups
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Dose Placebo | Total Body Drug Clearance (CL/F) of VP 20629 for Single Dose Groups | 1.010 liter per hour | Standard Deviation 0.171 |
| Single Dose VP 20629 150 mg | Total Body Drug Clearance (CL/F) of VP 20629 for Single Dose Groups | 1.533 liter per hour | Standard Deviation 0.209 |
| Single Dose VP 20629 450 mg | Total Body Drug Clearance (CL/F) of VP 20629 for Single Dose Groups | 1.956 liter per hour | Standard Deviation 0.196 |
| Single Dose VP 20629 900 mg | Total Body Drug Clearance (CL/F) of VP 20629 for Single Dose Groups | 2.357 liter per hour | Standard Deviation 0.447 |
Secondary
Volume of Distribution (Vz/F) of VP 20629 for Multiple Dose Groups
The Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours Postdose on Day 8
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Dose Placebo | Volume of Distribution (Vz/F) of VP 20629 for Multiple Dose Groups | 16.05 liter | Standard Deviation 5.28 |
| Single Dose VP 20629 150 mg | Volume of Distribution (Vz/F) of VP 20629 for Multiple Dose Groups | 19.77 liter | Standard Deviation 4.62 |
| Single Dose VP 20629 450 mg | Volume of Distribution (Vz/F) of VP 20629 for Multiple Dose Groups | 20.03 liter | Standard Deviation 2.98 |
Secondary
Volume of Distribution (Vz/F) of VP 20629 for Single Dose Groups
The Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1
Population: The pharmacokinetic set consisted of participants who had quantifiable VP 20629 plasma concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Dose Placebo | Volume of Distribution (Vz/F) of VP 20629 for Single Dose Groups | 15.0 Liter | Standard Deviation 3.4 |
| Single Dose VP 20629 150 mg | Volume of Distribution (Vz/F) of VP 20629 for Single Dose Groups | 17.6 Liter | Standard Deviation 2.9 |
| Single Dose VP 20629 450 mg | Volume of Distribution (Vz/F) of VP 20629 for Single Dose Groups | 20.8 Liter | Standard Deviation 6.1 |
| Single Dose VP 20629 900 mg | Volume of Distribution (Vz/F) of VP 20629 for Single Dose Groups | 26.9 Liter | Standard Deviation 6.3 |