Ignite Creation Date:
2024-05-05 @ 11:22 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00015808
Status:
COMPLETED
Last Update Posted:
2006-07-12
First Post:
2001-05-06
Brief Title:
Safety Study of Idebenone to Treat Friedreichs Ataxia
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase I Clinical Trial to Establish the Maximum Tolerated Dose of Idebenone in Children Adolescents and Adults 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 dose of idebonone that can safely be given to patients with Friedrichs ataxia an inherited degenerative disease that causes loss of muscle coordination speech problems weakness and sensory loss Enlargement of the left ventricle the large pumping chamber of the heart is also common in this disease In studies in France and Canada patients with Friedrichs ataxia who were given idebonone an antioxidant similar to the dietary supplement coenzyme Q had a decrease in the size of their left ventricle
Patients 5 years and older with Friedrichs ataxia may be eligible for this study Pregnant and lactating women may not participate Candidates will be screened with a medical history and physical examination and a review of genetic studies Patients who have not had genetic studies will be offered genetic counseling and testing to confirm or rule out Friedrichs ataxia
Participants will be admitted to the NIH Clinical Center for 3 days They will have blood and urine tests and a heart evaluation including an echocardiogram-a procedure that uses sound waves to produce images of the heart and an electrocardiogram-a study of the electrical activity of the heart When these tests have been completed patients will take an idebonone capsule They will be monitored for side effects for 72 hours Blood samples will be collected through an intravenous catheter flexible plastic tube placed in a vein 05 1 2 3 4 6 12 24 48 and 72 hours after the drug is taken to determine how long it takes for the drug to be eliminated from the body
Patients will return for a follow-up visit within 1 to 8 weeks Those who experienced no serious side effects may receive another higher dose of the drug with at least 6 days between doses
Patients 5 years and older with Friedrichs ataxia may be eligible for this study Pregnant and lactating women may not participate Candidates will be screened with a medical history and physical examination and a review of genetic studies Patients who have not had genetic studies will be offered genetic counseling and testing to confirm or rule out Friedrichs ataxia
Participants will be admitted to the NIH Clinical Center for 3 days They will have blood and urine tests and a heart evaluation including an echocardiogram-a procedure that uses sound waves to produce images of the heart and an electrocardiogram-a study of the electrical activity of the heart When these tests have been completed patients will take an idebonone capsule They will be monitored for side effects for 72 hours Blood samples will be collected through an intravenous catheter flexible plastic tube placed in a vein 05 1 2 3 4 6 12 24 48 and 72 hours after the drug is taken to determine how long it takes for the drug to be eliminated from the body
Patients will return for a follow-up visit within 1 to 8 weeks Those who experienced no serious side effects may receive another higher dose of the drug with at least 6 days between doses
Detailed Description:
Friedreichs ataxia FRDA is a progressive autosomal recessive multisystem degenerative disease for which there is currently no effective treatment Recent studies suggest that lipid-soluble antioxidants may prevent the progression of neurodegeneration and lead to some reversal of cardiomyopathy
This will be a phase Ia unblinded dose-escalation trial examining the toxicity and tolerability of the antioxidant idebenone in patients with FRDA Our primary objective is to determine the maximum tolerated single dose of idebenone in patients with FRDA Our secondary objective is to document the pharmacokinetics of single-dose idebenone in this population We aim to enroll 48 patients divided evenly among three age cohorts children ages 5-11 adolescents ages 12-17 and adults age greater than or equal to 18 Each age cohort will be studied independently Three patients from each cohort will receive one day of oral idebenone followed by inpatient monitoring for 72 hours If dose-limiting toxicity DLT is not observed during the 72-hour study period three new patients will receive the next highest dose If one of three patients experiences DLT three new patients will receive the same dose Within each cohort the dose will be escalated until the maximum tolerated dose MTD is established The MTD will be defined as one dose below that which resulted in DLT in any two patients within a cohort
Subsequent to the completion of this phase Ia trial we plan to further refine the MTD for each age group in a phase Ib trial in which we will examine multiple-dose regimens over a longer study period We hope to follow these phase I studies with a double-blinded placebo-controlled phase II trial to further evaluate safety and to estimate the efficacy of idebenone using cardiac parameters as our primary endpoints In addition we are currently in the process of validating a clinical evaluation scale for FRDA that we hope to employ in measuring neurological parameters as a secondary endpoint in the phase II trial
This will be a phase Ia unblinded dose-escalation trial examining the toxicity and tolerability of the antioxidant idebenone in patients with FRDA Our primary objective is to determine the maximum tolerated single dose of idebenone in patients with FRDA Our secondary objective is to document the pharmacokinetics of single-dose idebenone in this population We aim to enroll 48 patients divided evenly among three age cohorts children ages 5-11 adolescents ages 12-17 and adults age greater than or equal to 18 Each age cohort will be studied independently Three patients from each cohort will receive one day of oral idebenone followed by inpatient monitoring for 72 hours If dose-limiting toxicity DLT is not observed during the 72-hour study period three new patients will receive the next highest dose If one of three patients experiences DLT three new patients will receive the same dose Within each cohort the dose will be escalated until the maximum tolerated dose MTD is established The MTD will be defined as one dose below that which resulted in DLT in any two patients within a cohort
Subsequent to the completion of this phase Ia trial we plan to further refine the MTD for each age group in a phase Ib trial in which we will examine multiple-dose regimens over a longer study period We hope to follow these phase I studies with a double-blinded placebo-controlled phase II trial to further evaluate safety and to estimate the efficacy of idebenone using cardiac parameters as our primary endpoints In addition we are currently in the process of validating a clinical evaluation scale for FRDA that we hope to employ in measuring neurological parameters as a secondary endpoint in the phase II trial
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 |
|---|---|---|---|
| 01-N-0167 | None | None | None |