Ignite Creation Date:
2024-05-05 @ 11:34 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00078481
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2004-02-27
Brief Title:
Phase 1 Trial of Idebenone to Treat Patients With Friedreichs Ataxia
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase 1B Clinical Trial to Establish the Safety and Tolerability of a Multiple-Dose Regimen of Idebenone Administered to Patients With Friedreichs Ataxia
Status:
COMPLETED
Status Verified Date:
2006-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will determine the highest amount of idebenone that can be taken without harmful side effects in children teenagers and adults with Friedreichs ataxia a progressive degenerative disease that affects several body systems Studies in France and Canada showed that patients with Friedreichs ataxia who took idebenone had a decrease in the size of their left ventricle main pumping chamber of the heart which is often enlarged in this disease It is possible that idebenone may also prevent the progression of nervous system degeneration in Friedreichs ataxia
Patients 5 years of age and older with Friedreichs ataxia may be eligible for this study Candidates are screened with a blood test and review of their medical records including genetic studies
Participants undergo the following procedures during a 6-day hospital admission to the NIH Clinical Center
Placement of an intravenous catheter plastic tube inserted into a vein for collecting blood samples after drug administration
Blood and urine tests
Heart examination including electrocardiogram EKG to assess heart function and size
Idebenone therapy Patients take three tablets a day at 7 AM 1 PM and 7 PM on days 2 3 and 4 of hospitalization Blood samples are collected through the IV tube at 05 1 2 4 and 6 hours after the first dose on day 2 then at 1 hour after the first and third doses every day and then at 1 2 4 8 12 24 36 and 48 hours after the last dose on day 4 to determine how the body uses and eliminates the drug
Monitoring for drug side effects Patients have frequent checks of vital signs blood pressure pulse temperature breathing rate and a brief physical examination to check for drug side effects from the start of drug therapy on day 2 until at least 43 hours after the last dose on day 4
Patients who experience no difficulties are discharged from the hospital after the sixth day with a 1-month supply of medication to take 3 times a day at home They are contacted by phone every 2 weeks while taking the medication to check side effects Blood tests are also done every 2 weeks to check for any abnormalities
Patients 5 years of age and older with Friedreichs ataxia may be eligible for this study Candidates are screened with a blood test and review of their medical records including genetic studies
Participants undergo the following procedures during a 6-day hospital admission to the NIH Clinical Center
Placement of an intravenous catheter plastic tube inserted into a vein for collecting blood samples after drug administration
Blood and urine tests
Heart examination including electrocardiogram EKG to assess heart function and size
Idebenone therapy Patients take three tablets a day at 7 AM 1 PM and 7 PM on days 2 3 and 4 of hospitalization Blood samples are collected through the IV tube at 05 1 2 4 and 6 hours after the first dose on day 2 then at 1 hour after the first and third doses every day and then at 1 2 4 8 12 24 36 and 48 hours after the last dose on day 4 to determine how the body uses and eliminates the drug
Monitoring for drug side effects Patients have frequent checks of vital signs blood pressure pulse temperature breathing rate and a brief physical examination to check for drug side effects from the start of drug therapy on day 2 until at least 43 hours after the last dose on day 4
Patients who experience no difficulties are discharged from the hospital after the sixth day with a 1-month supply of medication to take 3 times a day at home They are contacted by phone every 2 weeks while taking the medication to check side effects Blood tests are also done every 2 weeks to check for any abnormalities
Detailed Description:
Background Friedreichs ataxia FRDA is a progressive autosomal recessive multisystem degenerative disease for which there is currently no effective treatment Recent studies have demonstrated that lipid-soluble antioxidants lead to a modest reversal of cardiomyopathy in patients with FRDA It is possible that antioxidants may also prevent the progression of neurodegeneration
Objective This will be a phase 1B unblinded trial examining the toxicity and tolerability of the antioxidant idebenone given as a multiple-dose regimen for a short inpatient course and then long term to patients with FRDA
Study Population We aim to enroll 15 patients divided evenly among three age cohorts children ages 5-11 adolescents ages 12-17 and adults age greater than or equal to 18
Design Our primary objective is to examine the tolerability of idebenone given at a dose of 60 mgkgday for 72 hours total of 9 doses in an inpatient setting NIH Clinical Center This dose is below the maximum dose examined 75 mgkgday that was well tolerated with no dose-limiting toxicity DLT in our phase 1A protocol 01-N-0167 study The 72 hour course represents 55 half-lives of the drug based upon previous studies of the drug in healthy human subjects and our phase 1A data thereby allowing the serum concentration of the drug to reach steady-state levels This multiple dose regimen will allow us to examine accumulation of the drug and to examine tolerability of the drug at a steady-state concentration The patients will then be followed by inpatient monitoring for an additional 43 hours representing 33 half-lives to allow relatively complete elimination of the drug If no adverse events are noted during the inpatient phase of the trial patients will resume taking the drug on an outpatient basis for 1 month to determine long-term tolerability and compliance Outpatients will be followed through phone interviews by the NIH research team along with routine blood work every 2 weeks Our secondary objective is to document the pharmacokinetics specifically the apparent distribution volume Vd elimination half-life t12 elimination clearance CLE and steady-state concentrations CSS of idebenone during the inpatient phase of the study
Outcome Parameters Outcomes in this phase I trial are types and frequency of adverse events if any and compliance with the dosing regimen Our secondary endpoint is pharmacokinetics of this dosing regimen
Future Directions We hope to follow these phase I studies with a multicenter double-blinded placebo-controlled phase III trial using an ataxia scale developed for FRDA as the primary endpoint
Objective This will be a phase 1B unblinded trial examining the toxicity and tolerability of the antioxidant idebenone given as a multiple-dose regimen for a short inpatient course and then long term to patients with FRDA
Study Population We aim to enroll 15 patients divided evenly among three age cohorts children ages 5-11 adolescents ages 12-17 and adults age greater than or equal to 18
Design Our primary objective is to examine the tolerability of idebenone given at a dose of 60 mgkgday for 72 hours total of 9 doses in an inpatient setting NIH Clinical Center This dose is below the maximum dose examined 75 mgkgday that was well tolerated with no dose-limiting toxicity DLT in our phase 1A protocol 01-N-0167 study The 72 hour course represents 55 half-lives of the drug based upon previous studies of the drug in healthy human subjects and our phase 1A data thereby allowing the serum concentration of the drug to reach steady-state levels This multiple dose regimen will allow us to examine accumulation of the drug and to examine tolerability of the drug at a steady-state concentration The patients will then be followed by inpatient monitoring for an additional 43 hours representing 33 half-lives to allow relatively complete elimination of the drug If no adverse events are noted during the inpatient phase of the trial patients will resume taking the drug on an outpatient basis for 1 month to determine long-term tolerability and compliance Outpatients will be followed through phone interviews by the NIH research team along with routine blood work every 2 weeks Our secondary objective is to document the pharmacokinetics specifically the apparent distribution volume Vd elimination half-life t12 elimination clearance CLE and steady-state concentrations CSS of idebenone during the inpatient phase of the study
Outcome Parameters Outcomes in this phase I trial are types and frequency of adverse events if any and compliance with the dosing regimen Our secondary endpoint is pharmacokinetics of this dosing regimen
Future Directions We hope to follow these phase I studies with a multicenter double-blinded placebo-controlled phase III trial using an ataxia scale developed for FRDA as the primary endpoint
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-N-0129 | None | None | None |