Back to resultsSafety and Pharmacology Study of VP 20629 in Adults With Friedreich's Ataxia
Primary Purpose
Friedreich's Ataxia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
VP 20629
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Friedreich's Ataxia
Eligibility Criteria
Inclusion Criteria:
- Be 18 to 45 years of age (inclusive).
- Have a body mass index between 18 and 27 kg/m^2 (inclusive).
- Have a clinical presentation consistent with FA.
- Have a confirmed diagnosis of FA with a defined expanded guanosine, adenine, adenine (GAA) triplet repeat number.
- Have an International Cooperative Ataxia Rating Scale (ICARS) mean total score of ≤75.
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.
- Be able to swallow capsules whole.
- Agree to adhere to the protocol-defined schedule of assessments and procedures.
- Be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.
Exclusion Criteria:
- 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.
- If female, be pregnant or breastfeeding.
- Have a positive test result for human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C antibody.
- 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.
- 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).
- Have a known hypersensitivity to any ingredient in the study formulation.
- 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.
- Have a Columbia-Suicide Severity Rating Scale (C-SSRS) score of 4 or 5.
Sites / Locations
- UCLA Medical Center
- University of South Florida
- Emory University
- University of Iowa Children's Hospital
- Children's Hospital of Philadelphia
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Single dose of VP 20629 or placebo
Multiple doses of VP 20629 or placebo
Arm Description
Four groups of 8 subjects each will receive a single dose of VP 20629 (150 mg, 450 mg, 900 mg, or 1200 mg) or placebo.
Three groups of 8 subjects each will receive multiple doses of VP 20629 (300 mg, 600 mg, or 900 mg total daily dose) or placebo. VP 20629 or placebo will be administered every 8 hours for 7 days with a single morning dose on Day 8.
Outcomes
Primary Outcome Measures
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).
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.
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.
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.
Secondary Outcome Measures
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 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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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 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 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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01898884
Brief Title
Safety and Pharmacology Study of VP 20629 in Adults With Friedreich's Ataxia
Official Title
A Phase 1, Randomized, Double-blind, Placebo-controlled, Multicenter, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral VP 20629 in Adult Subjects With Friedreich's Ataxia
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
August 13, 2013 (Actual)
Primary Completion Date
June 18, 2015 (Actual)
Study Completion Date
June 18, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire
4. Oversight
Data Monitoring Committee
No
5. Study Description
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]
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Friedreich's Ataxia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single dose of VP 20629 or placebo
Arm Type
Experimental
Arm Description
Four groups of 8 subjects each will receive a single dose of VP 20629 (150 mg, 450 mg, 900 mg, or 1200 mg) or placebo.
Arm Title
Multiple doses of VP 20629 or placebo
Arm Type
Experimental
Arm Description
Three groups of 8 subjects each will receive multiple doses of VP 20629 (300 mg, 600 mg, or 900 mg total daily dose) or placebo. VP 20629 or placebo will be administered every 8 hours for 7 days with a single morning dose on Day 8.
Intervention Type
Drug
Intervention Name(s)
VP 20629
Other Intervention Name(s)
Indole-3-propionic acid
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Description
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
Title
Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Description
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
Title
Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Description
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
Title
Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs)
Description
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
Secondary Outcome Measure Information:
Title
Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups
Description
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
Title
Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups
Description
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
Title
Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups
Description
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
Title
Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups
Description
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
Title
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
Description
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
Title
Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups
Description
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
Title
Volume of Distribution (Vz/F) of VP 20629 for Single Dose Groups
Description
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
Title
Total Body Drug Clearance (CL/F) of VP 20629 for Single Dose Groups
Description
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
Title
Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups
Description
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
Title
Cumulative Amount Excreted Into the Urine (Ae) for Unchanged VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups
Description
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
Title
Percentage of Drug Excreted in Urine (Ae%) of VP 20629 for Single Dose Groups
Description
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
Title
Renal Clearance (CLR) of VP 20629 for Single Dose Groups
Description
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
Title
Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
Description
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
Title
Maximum Observed Serum Concentration at Steady State (Cmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
Description
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
Title
Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
Description
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
Title
Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
Description
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
Title
Area Under the Plasma Concentration Versus Time Curve (AUC) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
Description
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
Title
Area Under the Plasma Concentration Versus Time Curve at Steady State (AUCss) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
Description
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
Title
Area Under the Plasma Concentration Versus Time Curve (AUC[0-8]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
Description
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
Title
Area Under the Plasma Concentration Versus Time Curve (AUCt) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
Description
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
Title
Terminal Plasma Half-Life (t1/2) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
Description
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
Title
Volume of Distribution (Vz/F) of VP 20629 for Multiple Dose Groups
Description
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
Title
Total Body Drug Clearance at Steady State (CLss/F) of VP 20629 for Multiple Dose Groups
Description
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
Title
Elimination Rate Constant (Lambda[z]) of VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
Description
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
Title
Cumulative Amount Excreted Into the Urine at Steady State (Ae,ss) of Unchanged VP 20629 and Its Metabolite (VP 20631) for Multiple Dose Groups
Description
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
Title
Percentage of Drug Excreted in Urine at Steady-State (Ae%,ss) of VP 20629 for Multiple Dose Groups
Description
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
Title
Renal Clearance at Steady State (CLR,ss) of VP 20629 for Multiple Dose Groups
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Be 18 to 45 years of age (inclusive).
Have a body mass index between 18 and 27 kg/m^2 (inclusive).
Have a clinical presentation consistent with FA.
Have a confirmed diagnosis of FA with a defined expanded guanosine, adenine, adenine (GAA) triplet repeat number.
Have an International Cooperative Ataxia Rating Scale (ICARS) mean total score of ≤75.
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.
Be able to swallow capsules whole.
Agree to adhere to the protocol-defined schedule of assessments and procedures.
Be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.
Exclusion Criteria:
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.
If female, be pregnant or breastfeeding.
Have a positive test result for human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C antibody.
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.
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).
Have a known hypersensitivity to any ingredient in the study formulation.
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.
Have a Columbia-Suicide Severity Rating Scale (C-SSRS) score of 4 or 5.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Name
University of Iowa Children's Hospital
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety and Pharmacology Study of VP 20629 in Adults With Friedreich's Ataxia
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